+

WO2013170115A1 - Dérivés de pyridazine et pyridine en tant qu'inhibiteurs de nampt - Google Patents

Dérivés de pyridazine et pyridine en tant qu'inhibiteurs de nampt Download PDF

Info

Publication number
WO2013170115A1
WO2013170115A1 PCT/US2013/040481 US2013040481W WO2013170115A1 WO 2013170115 A1 WO2013170115 A1 WO 2013170115A1 US 2013040481 W US2013040481 W US 2013040481W WO 2013170115 A1 WO2013170115 A1 WO 2013170115A1
Authority
WO
WIPO (PCT)
Prior art keywords
carboxamide
phenyl
pyridazin
azetidine
piperidin
Prior art date
Application number
PCT/US2013/040481
Other languages
English (en)
Inventor
Todd M. Hansen
Kenton Longenecker
Howard R. Heyman
Michael L. Curtin
Richard F. Clark
Bryan Sorensen
Zhiqin Ji
George Doherty
Robin Frey
Kevin Woller
Original Assignee
Abbvie Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Abbvie Inc. filed Critical Abbvie Inc.
Priority to EP13726339.8A priority Critical patent/EP2847181A1/fr
Priority to JP2015511730A priority patent/JP2015520752A/ja
Priority to CA2873097A priority patent/CA2873097A1/fr
Priority to CN201380036867.6A priority patent/CN104583194A/zh
Priority to MX2014013751A priority patent/MX2014013751A/es
Publication of WO2013170115A1 publication Critical patent/WO2013170115A1/fr
Priority to HK15110586.2A priority patent/HK1209739A1/xx

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/04—Antipruritics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Definitions

  • This invention pertains to compounds which inhibit the activity of NAMPT, compositions containing the compounds, and methods of treating diseases during which NAMPT is expressed.
  • NAD+ (nicotinamide adenine dinucleotide) is a coenzyme that plays a critical role in many physiologically essential processes (Ziegkel, M. Eur. J. Biochem. 267,1550-1564, 2000). NAD is necessary for several signaling pathways including among others poly ADP- ribosylation in DNA repair, mono-ADP-ribosylation in both the immune system and G- protein-coupled signaling, and NAD is also required by sirtuins for their deacetylase activity (Garten, A. et al Trends in Endocrinology and Metabolism, 20, 130-138, 2008).
  • NAMPT also known as pre-B-cell-colony-enhancing factor (PBEF) and visfatin
  • PBEF pre-B-cell-colony-enhancing factor
  • visfatin is an enzyme that catalyzes the phosphoribosylation of nicotinamide and is the rate-limiting enzyme in one of two pathways that salvage NAD.
  • NAMPT inhibitors have potential as anticancer agents. Cancer cells have a higher basal turnover of NAD and also display higher energy requirements compared with normal cells. Additionally, increased NAMPT expression has been reported in colorectal cancer (Van Beijnum, J.R. et al Int. J. Cancer 101, 1 18-127, 2002) and NAMPT is involved in angiogenesis (Kim, S.R. et al. Biochem. Biophys. Res. Commun. 357, 150-156, 2007). Small-molecule inhibitors of NAMPT have been shown to cause depletion of intracellular NAD+ levels and ultimately induce tumor cell death (Hansen, CM et al. Anticancer Res. 20, 421 1 1 -4220, 2000) as well as inhibit tumor growth in xenograft models (Olese, U.H. et al. Mol Cancer Ther. 9, 1609-1617, 2010).
  • NAMPT inhibitors also have potential as therapeutic agents in inflammatory and metabolic disorders (Galli, M. et al Cancer Res. 70, 8- 1 1, 2010).
  • NAMPT is the predominant enzyme in T and B lymphocytes.
  • Selective inhibition of NAMPT leads to NAD+ depletion in lymphocytes blocking the expansion that accompanies autoimmune disease progression whereas cell types expressing the other NAD+ generating pathways might be spared.
  • a small molecule NAMPT inhibitor (FK866) has been shown to selectively block proliferation and induce apoptosis of activated T cells and was efficacious in animal models of arthritis (collagen -induced arthritis) (Busso, N.et al. Plos One 3, e2267, 2008).
  • FK866 ameliorated the manifestations of experimental autoimmune encephalomyelitis (EAE), a model of T-cell mediated autoimmune disorders.
  • EAE experimental autoimmune encephalomyelitis
  • NaMPT activity increases NF-kB transcriptional activity in human vascular endothelial cell, resulting in MMP-2 and MMP-9 activation, suggesting a role for NAMPT inhibitors in the prevention of inflammatory mediated complications of obesity and type 2 diabetes (Adya, R. et. Al. Diabetes Care, 31, 758-760, 2008).
  • X 1 is N and X 2 is CR 1 ;
  • X 1 is CR 1 and X 2 is N;
  • X 1 is CR 1 and X 2 is CR 1 ;
  • Y 1 is C(0)NH, or NHC(O);
  • Z 1 is wherein indicates the point of attachment to Y 1 and x ⁇ indicates the point of attachment to the nitrogen containing heteroaryl;
  • R 1 at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH 2 , CN, N0 2 , F, CI, Br and I;
  • R 2 is independently selected from the group consisting of CzpCe-alkyl, CzpCe-alkenyl, CzrC 6 -alkynyl, aryl, and 5-6 membered heteroaryl; wherein each R 2 CzpCe-alkyl, C4-C6- alkenyl, and CzpCe-alkynyl is substituted with one or more substituents independently selected from the group consisting of R 3 , OR 3 , SR 3 , S(0)R 3 , S0 2 R 3 , C(0)R 3 , CO(0)R 3 , OC(0)R 3 , OC(0)OR 3 , NH 2 , NHR 3 , N(R 3 ) 2 , NHC(0)R 3 , NR 3 C(0)R 3 , NHS(0) 2 R 3 , NR 3 S(0) 2 R 3 ,
  • NHC(0)OR 3 NR 3 C(0)OR 3 , NHC(0)NH 2 , NHC(0)NHR 3 , NHC(0)N(R 3 ) 2 , NR 3 C(0)NHR 3 , NR 3 C(0)N(R 3 ) 2 , C(0)NH 2 , C(0)NHR 3 , C(0)N(R 3 ) 2 , C(0)NHOH, C(0)NHOR 3 ,
  • each R 2 aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R 4 , OR 4 , SR 4 , S(0)R 4 , S0 2 R 4 , C(0)R 4 , OC(0)OR 4 , NH 2 , NHR 4 , N(R 4 ) 2 , NHC(0)R 4 , NR 4 C(0)R 4 , NHS(0) 2 R 4 , NR 4 S(0) 2 R 4 , NHC(0)OR 4 , NR 4 C(0)OR 4 , NHC(0)NH 2 , NHC(0)NHR 4 , NHC(0)N(R 4 ) 2 , NR 4 C(0)NHR 4 , NR 4 C(0)N(
  • R 3 is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and heterocyclyl; wherein each R 3 alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R 5 , OR 5 , SR 5 , S(0)R 5 , S0 2 R 5 , C(0)R 5 , CO(0)R 5 , OC(0)R 5 , OC(0)OR 5 , NH 2 , NHR 5 , N(R 5 ) 2 , NHC(0)R 5 , NR 5 C(0)R 5 , NHS(0) 2 R 5 ,
  • R 4 is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R 4 alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R 7 , OR 7 , SR 7 , S(0)R 7 , S0 2 R 7 , C(0)R 7 , CO(0)R 7 , OC(0)R 7 , OC(0)OR 7 , NH 2 , NHR 7 , N(R 7 ) 2 , NHC(0)R 7 , NR 7 C(0)R 7 , NHS(0) 2 R 7 ,
  • C(0)NHOR 7 C(0)NHS0 2 R 7 , C(0)NR 7 S0 2 R 7 , S0 2 NH 2 , S0 2 NHR 7 , S0 2 N(R 7 ) 2 , C(0)H, C(0)OH, C(N)NH 2 , C(N)NHR 7 , C(N)N(R 7 ) 2 , CNOH, CNOCH 3 , OH, (O), CN, N 3 , N0 2 , F, CI, Br and I;
  • R 5 is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R 5 alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R 8 , OR 8 , SR 8 , S(0)R 8 , S0 2 R 8 , NHR 8 , N(R 8 ) 2 , C(0)R 8 , C(0)NH 2 , C(0)NHR 8 , C(0)N(R 8 ) 2 , NHC(0)R 8 , NR 8 C(0)R 8 , NHS0 2 R 8 , NHC(0)OR 8 , S0 2 NH 2 , S0 2 NHR 8 , S0 2 N(R 8 ) 2 , NHC(0)NH 2 , NHC(0)NHR 8 , OH, (O), C(0)OH, N 3 ,
  • R 6 is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R 6 alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R 9 , OR 9 , SR 9 , S(0)R 9 , S0 2 R 9 , NHR 9 , N(R 9 ) 2 , C(0)R 9 , C(0)NH 2 , C(0)NHR 9 , C(0)N(R 9 ) 2 , NHC(0)R 9 , NR 9 C(0)R 9 , NHS0 2 R 9 , NHC(0)OR 9 ,
  • R 7 is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;
  • R 8 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl
  • R 9 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;
  • R 10 independently optionally substituted with one or more substituents independently selected from the group consisting of R 10 , OR 10 , SR 10 , S(0)R 10 , S0 2 R 10 , C(0)R 10 , CO(0)R 10 , OC(0)R 10 , OC(0)OR 10 , C(0)C(0)R 10 , NH 2 , NHR 10 , N(R 10 ) 2 , NHC(0)R 10 , NR 10 C(O)R 10 , NHS(0) 2 R 10 , NR 10 S(O) 2 R 10 , NHC(0)OR 10 , NR 10 C(O)OR 10 , NHC(0)NH 2 , NHC(0)NHR 10 , NHC(O)N(R 10 ) 2 , NR 10 C(O)NHR 10 , NR 10 C(O)N(R 10 ) 2 , C(0)NH 2 , C(0)NHR 10 , C(O)N(R 10 ) 2 , C(0)NHOH, C(0)NHOR 10 , C(0)NH
  • R 10 is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R 10 alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R 11 , OR 11 , SR 11 , S(0)R u , S0 2 R u , C(0)R u , CO(0)R u , OC(0)R u , OC(0)OR u , NH 2 , NHR 11 , N(R U ) 2 , NHC(0)R u , NR u C(0)R u , NHS(0) 2 R u , NR u S(0) 2 R u , NHC(0)OR u , NR u C(0)OR u , NHC(0)NH 2 , NHC(0)NHR u ,
  • R 11 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R 11 alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R 11 aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R 13 , OR 13 , C(0)OR 13 , OCF 3 , CF 3 , F, CI, Br and I;
  • R 12 at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and R , at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;
  • R 2 pyrrolyl is not substituted with two alkyl groups.
  • Z 1 is
  • Z 1 is • - i innrdliircates the point of attachment to Y 1 and %N indicates the point of attachment to the nitrogen containing heteroaryl; and Y 1 is C(0)NH.
  • Z 1 is
  • i innrdliifcate the point of attachment to Y 1 and indicates the point of attachment to the nitrogen containing heteroaryl
  • Y 1 is C(0)NH
  • Z 1 is
  • Y 1 and ⁇ indicates the point of attachment to the nitrogen containing heteroaryl; Y 1 is C(0)NH; X 1 is N and X 2 is CR 1 ; wherein R 2 is phenyl; wherein each R 2 phenyl is substituted with one substituent independently selected from the group consisting of R 4 , OR 4 , and S0 2 R 4 .
  • IC rmula
  • Y 1 is C(0)NH
  • X 1 is N and X 2 is CR 1
  • R 2 is phenyl; wherein each R 2 phenyl is substituted with one substituent independently selected from the group consisting of R , OR , and SO 2 R .
  • Y 1 indicates the point of attachment to Y 1 and indicates the point of attachment to the nitrogen containing heteroaryl
  • Y 1 is C(0)NH
  • X 1 is N and X 2 is CR 1 ;
  • R 2 is phenyl; wherein each R 2 phenyl is substituted with one substituent independently selected from the group consisting of R 4 , OR 4 , and S0 2 R 4 ; and R 1 ,
  • Z 1 is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl
  • i innrdliir cates the point of attachment to Y 1 and indicates the point of attachment to the nitrogen containing heteroaryl
  • Y 1 is C(0)NH
  • X 1 is N and X 2 is CR 1
  • R 2 is phenyl; wherein each R 2 phenyl is substituted with one substituent independently selected from the group consisting of R 4 , OR 4 , and SO 2 R 4 ;
  • R 1 at each occurrence, is hydrogen; and R 4 , at each occurrence, is heterocyclyl.
  • vs- i innrdliir cates the point of attachment to Y 1 and ⁇ indicates the point of attachment to the nitrogen containing heteroaryl
  • Y 1 is C(0)NH
  • X 1 is N and X 2 is CR 1
  • R 2 is phenyl; wherein each R 2 phenyl is substituted with one substituent independently selected from the group consisting of R 4 , OR 4 , and SO 2 R 4 ; and R 1 , at each occurrence, is hydrogen; and R 4 , at each occurrence, is heterocyclyl.
  • Still another embodiment pertains to compounds, which are

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Diabetes (AREA)
  • Oncology (AREA)
  • Rheumatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Hematology (AREA)
  • Pulmonology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Dermatology (AREA)
  • Communicable Diseases (AREA)
  • Virology (AREA)
  • Neurology (AREA)
  • Obesity (AREA)
  • Urology & Nephrology (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Hospice & Palliative Care (AREA)
  • AIDS & HIV (AREA)
  • Pain & Pain Management (AREA)
  • Psychiatry (AREA)
  • Molecular Biology (AREA)

Abstract

L'invention concerne des composés de la formule (IC), ou un sel de qualité thérapeutique de ceux-ci, qui inhibent l'activité de NAMPT, des compositions contenant les composés et des méthodes de traitement de maladies au cours desquelles NAMPT est exprimé.
PCT/US2013/040481 2012-05-11 2013-05-10 Dérivés de pyridazine et pyridine en tant qu'inhibiteurs de nampt WO2013170115A1 (fr)

Priority Applications (6)

Application Number Priority Date Filing Date Title
EP13726339.8A EP2847181A1 (fr) 2012-05-11 2013-05-10 Dérivés de pyridazine et pyridine en tant qu'inhibiteurs de nampt
JP2015511730A JP2015520752A (ja) 2012-05-11 2013-05-10 Ｎａｍｐｔ阻害薬としてのピリダジンおよびピリジン誘導体
CA2873097A CA2873097A1 (fr) 2012-05-11 2013-05-10 Derives de pyridazine et pyridine en tant qu'inhibiteurs de nampt
CN201380036867.6A CN104583194A (zh) 2012-05-11 2013-05-10 作为nampt抑制剂的哒嗪和吡啶衍生物
MX2014013751A MX2014013751A (es) 2012-05-11 2013-05-10 Piridazina y derivados de piridina como inhibidores de nampt.
HK15110586.2A HK1209739A1 (en) 2012-05-11 2015-10-28 Pyridazine and pyridine derivatives as nampt inhibitors nampt

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US201261645692P 2012-05-11 2012-05-11
US61/645,692 2012-05-11
US201261719013P 2012-10-26 2012-10-26
US61/719,013 2012-10-26
US201361779756P 2013-03-13 2013-03-13
US61/779,756 2013-03-13

Publications (1)

Publication Number Publication Date
WO2013170115A1 true WO2013170115A1 (fr) 2013-11-14

Family

ID=48539390

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2013/040481 WO2013170115A1 (fr) 2012-05-11 2013-05-10 Dérivés de pyridazine et pyridine en tant qu'inhibiteurs de nampt

Country Status (11)

Country Link
US (4) US8975398B2 (fr)
EP (1) EP2847181A1 (fr)
JP (1) JP2015520752A (fr)
CN (1) CN104583194A (fr)
AR (1) AR091023A1 (fr)
CA (1) CA2873097A1 (fr)
HK (1) HK1209739A1 (fr)
MX (1) MX2014013751A (fr)
TW (1) TW201350478A (fr)
UY (1) UY34804A (fr)
WO (1) WO2013170115A1 (fr)

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9796712B2 (en) 2014-06-19 2017-10-24 Ariad Pharmaceuticals, Inc. Heteroaryl compounds for kinase inhibition
WO2018124001A1 (fr) 2016-12-27 2018-07-05 国立研究開発法人理化学研究所 Composé inhibiteur de signal bmp
WO2018177993A1 (fr) 2017-03-31 2018-10-04 Bayer Cropscience Aktiengesellschaft Pyrazoles pour lutter contre les arthropodes
US10144742B2 (en) 2014-04-18 2018-12-04 Millennium Pharmaceuticals, Inc. Quinoxaline compounds and uses thereof
US10323018B2 (en) 2015-01-20 2019-06-18 Millennium Pharmaceuticals, Inc. Quinazoline and quinoline compounds and uses thereof
US10710986B2 (en) 2018-02-13 2020-07-14 Gilead Sciences, Inc. PD-1/PD-L1 inhibitors
WO2020179859A1 (fr) 2019-03-06 2020-09-10 第一三共株式会社 Dérivé de pyrrolopyrazole
US10774071B2 (en) 2018-07-13 2020-09-15 Gilead Sciences, Inc. PD-1/PD-L1 inhibitors
US10899735B2 (en) 2018-04-19 2021-01-26 Gilead Sciences, Inc. PD-1/PD-L1 inhibitors
US11021514B2 (en) 2016-06-01 2021-06-01 Athira Pharma, Inc. Compounds
US11236085B2 (en) 2018-10-24 2022-02-01 Gilead Sciences, Inc. PD-1/PD-L1 inhibitors
US11345681B1 (en) 2020-06-05 2022-05-31 Kinnate Biopharma Inc. Inhibitors of fibroblast growth factor receptor kinases
US11638762B2 (en) 2016-10-18 2023-05-02 Seagen Inc. Targeted delivery of nicotinamide adenine dinucleotide salvage pathway inhibitors
US11807626B2 (en) 2020-04-23 2023-11-07 Opna Bio SA Compounds and methods for CD73 modulation and indications therefor
US11931414B2 (en) 2017-04-27 2024-03-19 Seagen Inc. Quaternized nicotinamide adenine dinucleotide salvage pathway inhibitor conjugates
US12084431B2 (en) 2018-05-14 2024-09-10 Takeda Pharmaceutical Company Limited Pharmaceutical salts of pyrimidine derivatives and method of treating disorders

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104583194A (zh) * 2012-05-11 2015-04-29 艾伯维公司 作为nampt抑制剂的哒嗪和吡啶衍生物
CA2942101A1 (fr) 2014-03-21 2015-09-24 Abbvie Inc. Anticorps anti-egfr et conjugues anticorps-medicament
MX385778B (es) 2014-04-04 2025-03-18 Del Mar Pharmaceuticals Uso de dianhidrogalactitol y análogos o derivados del mismo para tratar cáncer de células no pequeñas del pulmón y cáncer de ovario.
MX2018015284A (es) 2016-06-08 2019-09-18 Abbvie Inc Conjugados de anticuerpo anti-egfr y fármaco.
UA124198C2 (uk) 2016-06-08 2021-08-04 Еббві Інк. Кон'югат антитіла до в7-н3 та лікарського засобу
EP3469000A1 (fr) 2016-06-08 2019-04-17 AbbVie Inc. Anticorps anti-b7-h3 et conjugués anticorps-médicaments
BR112018075645A2 (pt) 2016-06-08 2019-04-09 Abbvie Inc. conjugados de anticorpo fármaco anti-egfr
CA3027033A1 (fr) 2016-06-08 2017-12-14 Abbvie Inc. Anticorps anti-cd98 et conjugues anticorps-medicament
AU2017279539A1 (en) 2016-06-08 2019-01-03 Abbvie Inc. Anti-B7-H3 antibodies and antibody drug conjugates
KR102459256B1 (ko) * 2016-06-23 2022-10-25 세인트 쥬드 칠드런즈 리써치 호스피탈, 인코포레이티드 판토테네이트 키나제의 소분자 조절제
WO2018195302A1 (fr) 2017-04-19 2018-10-25 Bluefin Biomedicine, Inc. Anticorps anti-vtcn1 et conjugués anticorps-médicament
CN111818922B (zh) 2017-12-27 2023-06-13 圣朱德儿童研究医院有限公司 泛酸激酶的小分子调节剂
JP7527967B2 (ja) 2017-12-27 2024-08-05 セント ジュード チルドレンズ リサーチ ホスピタル，インコーポレイティド Ｃａｓｔｏｒに関連する障害を治療する方法
EP3746079A1 (fr) * 2018-01-31 2020-12-09 Bayer Aktiengesellschaft Conjugués anticorps-médicament (adc) avec des inhibiteurs de nampt
US20210388018A1 (en) * 2018-10-01 2021-12-16 Cornell University Methyl and ethyl nicotinate-riboside-5-phosphates, preparation thereof and methods of use thereof
EP3997209A4 (fr) * 2019-07-08 2023-06-07 Mayo Foundation for Medical Education and Research Activateurs de wnt et procédés d'utilisation
CN114660219A (zh) * 2020-12-23 2022-06-24 安徽古特生物科技有限公司 一种β-烟酰胺单核苷酸的检测方法
AR124681A1 (es) 2021-01-20 2023-04-26 Abbvie Inc Conjugados anticuerpo-fármaco anti-egfr
WO2024127366A1 (fr) 2022-12-16 2024-06-20 Pheon Therapeutics Ltd Anticorps dirigés contre la protéine 1 contenant le domaine cub (cdcp1) et leurs utilisations
CN117285573B (zh) * 2023-09-26 2024-03-26 长沙兴嘉生物工程股份有限公司 一种β-烟酰胺单核苷酸金属络合物及其制备方法

Citations (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995007271A1 (fr) 1993-09-09 1995-03-16 The Upjohn Company Agents antimicrobiens oxazolidinone a substitution oxazine et thiazine
WO1997010223A1 (fr) 1995-09-15 1997-03-20 Pharmacia & Upjohn Company Aminoryle oxazolidinone n-oxydes
WO2003074500A2 (fr) * 2002-03-06 2003-09-12 Sanofi-Aventis Nouveaux composes
WO2005016915A1 (fr) * 2003-08-14 2005-02-24 Glaxo Group Limited Derives carboxamides de piperidine/cyclohexane destines a etre utilises comme modulateurs du recepteur vanilloide
WO2005099353A2 (fr) 2004-04-19 2005-10-27 Symed Labs Limited Nouveau procede pour preparer du linezolide et des composes associes
WO2006008754A1 (fr) 2004-07-20 2006-01-26 Symed Labs Limited Nouveaux intermediaires pour linezolide et composes correspondants
EP1700856A1 (fr) * 2003-12-26 2006-09-13 Kyowa Hakko Kogyo Co., Ltd. Derive de thiazole
US20090082471A1 (en) 2007-09-26 2009-03-26 Protia, Llc Deuterium-enriched fingolimod
US7511013B2 (en) 2004-09-29 2009-03-31 Amr Technology, Inc. Cyclosporin analogues and their pharmaceutical uses
US20090088416A1 (en) 2007-09-26 2009-04-02 Protia, Llc Deuterium-enriched lapaquistat
US7514068B2 (en) 2005-09-14 2009-04-07 Concert Pharmaceuticals Inc. Biphenyl-pyrazolecarboxamide compounds
US20090093422A1 (en) 2006-10-23 2009-04-09 Roger Tung Oxazolidinone derivatives and methods of use
US7521421B2 (en) 1997-10-08 2009-04-21 Isotechnika Inc. Deuterated cyclosporine analogs and methods of making the same
US20090105338A1 (en) 2007-10-18 2009-04-23 Protia, Llc Deuterium-enriched gabexate mesylate
US20090105147A1 (en) 2007-10-18 2009-04-23 Concert Pharmaceuticals Inc. Deuterated etravirine
US20090105307A1 (en) 2007-02-15 2009-04-23 Guido Galley 2-aminooxazolines as taar1 ligands
US20090111840A1 (en) 2005-05-31 2009-04-30 Peter Herold Heterocyclic spiro-compounds as aldosterone synthase inhibitors
US7528131B2 (en) 2007-04-19 2009-05-05 Concert Pharmaceuticals Inc. Substituted morpholinyl compounds
US20090118238A1 (en) 2007-09-17 2009-05-07 Protia, Llc Deuterium-enriched alendronate
US7531685B2 (en) 2007-06-01 2009-05-12 Protia, Llc Deuterium-enriched oxybutynin
US7534814B2 (en) 1999-07-30 2009-05-19 Nabriva Therapeutics Ag Mutilin derivatives and their use as antibacterials
US20090131485A1 (en) 2007-09-10 2009-05-21 Concert Pharmaceuticals, Inc. Deuterated pirfenidone
US20090131363A1 (en) 2007-10-26 2009-05-21 Harbeson Scott L Deuterated darunavir
US20090137457A1 (en) 2007-10-02 2009-05-28 Concert Pharmaceuticals, Inc. Pyrimidinedione derivatives
WO2011025799A1 (fr) * 2009-08-26 2011-03-03 Glaxo Group Limited Inhibiteurs de cathepsine c
WO2012031199A1 (fr) * 2010-09-03 2012-03-08 Forma Therapeutics, Inc. Composés et compositions de guanidine pour l'inhibition de nampt

Family Cites Families (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3088016B2 (ja) 1993-03-29 2000-09-18 ゼネカ・リミテッド 血小板凝集抑制剤としての複素環式化合物
IL115420A0 (en) 1994-09-26 1995-12-31 Zeneca Ltd Aminoheterocyclic derivatives
DE19624668A1 (de) 1996-06-20 1998-02-19 Klinge Co Chem Pharm Fab Verwendung von Pyridylalkan-, Pyridylalken- bzw. Pyridylalkinsäureamiden
DE19624659A1 (de) 1996-06-20 1998-01-08 Klinge Co Chem Pharm Fab Neue Pyridylalken- und Pyridylalkinsäureamide
US6372759B1 (en) 1997-06-26 2002-04-16 Eli Lilly And Company Antithrombotic agents
CA2294042A1 (fr) 1997-06-26 1999-01-07 David Kent Herron Agents antithrombotiques
GB0010757D0 (en) 2000-05-05 2000-06-28 Astrazeneca Ab Chemical compounds
CA2416384A1 (fr) 2000-07-17 2003-01-16 Takeda Chemical Industries, Ltd. Derives de sulfonate, leur production et utilisation
MXPA04001144A (es) 2001-08-07 2004-07-08 Banyu Pharma Co Ltd Compuestos espiro.
DK1485348T3 (da) 2002-03-13 2008-09-29 Janssen Pharmaceutica Nv Carbonylamino-derivater som nye inhibitorer af histandeacetylase
EP1348434A1 (fr) 2002-03-27 2003-10-01 Fujisawa Deutschland GmbH Utilisation de pyridylamides comme inhibiteurs de l'angiogenèse
AU2004276337B2 (en) 2003-09-24 2009-11-12 Methylgene Inc. Inhibitors of histone deacetylase
US7244735B2 (en) 2003-12-02 2007-07-17 Vertex Pharmaceuticals Inc. Heterocyclic protein kinase inhibitors and uses thereof
WO2006058338A2 (fr) 2004-11-29 2006-06-01 Janssen Pharmaceutica N.V. Modulateurs de 4-piperidinecarboxamide du recepteur vanilloide vr1
BRPI0608553A2 (pt) * 2005-02-24 2010-01-12 Millennium Pharm Inc antagonistas de receptor de pgd2 para o tratamento de doenças inflamatórias
EP1861396A1 (fr) 2005-03-04 2007-12-05 AstraZeneca AB Derives tricycliques d'azetidine et de pyrrole a activite antibacterienne
WO2007076055A2 (fr) * 2005-12-22 2007-07-05 Entremed, Inc. Compositions et methodes comprenant l'utilisation d'antagonistes du recepteur active par des proteases
TW200800997A (en) 2006-03-22 2008-01-01 Astrazeneca Ab Chemical compounds
TW200815426A (en) 2006-06-28 2008-04-01 Astrazeneca Ab New pyridine analogues II 333
WO2008026018A1 (fr) 2006-09-01 2008-03-06 Topotarget Switzerland Sa Nouveau procédé pour le traitement des maladies inflammatoires
ES2565683T3 (es) * 2006-09-15 2016-04-06 Xcovery, Inc. Compuestos inhibidores de quinasa
EP2129660A2 (fr) * 2006-12-19 2009-12-09 Pfizer Products Inc. Dérivés de nicotinamide en tant qu'inhibiteurs de h-pgds et leur utilisation pour le traitement de maladies liées aux prostaglandines d2
US20090113874A1 (en) 2007-11-02 2009-05-07 Caterpillar Inc. System and method for electrically regenerating a particulate filter assembly of a generator set
NZ587719A (en) 2008-02-26 2012-04-27 Takeda Pharmaceutical Fused heterocyclic derivative and use thereof
EP2098231A1 (fr) 2008-03-05 2009-09-09 Topotarget Switzerland SA Utilisation des inhibiteurs de la formation de NAD pour le traitement de lesions d'ischemie-reperfusion
WO2009153197A1 (fr) 2008-06-18 2009-12-23 F. Hoffmann-La Roche Ag Pyrimidodiazépines à substitution halogéno en tant qu’inhibiteurs de plkl
EP2379535B1 (fr) 2008-12-22 2016-06-15 Array Biopharma Inc. Dérivés d'acide 7-phénoxychromanecarboxylique
US9499533B2 (en) * 2012-03-27 2016-11-22 Shionogi & Co., Ltd. Aromatic 5-membered heterocyclic derivative having TRPV4-Inhibiting activity
WO2013144180A1 (fr) * 2012-03-28 2013-10-03 Intervet International B.V. Composés hétéroaryles à unité de pontage cyclique utilisés dans le traitement d'infections helminthiques
US9296723B2 (en) * 2012-05-11 2016-03-29 Abbvie Inc. NAMPT inhibitors
CN104583194A (zh) * 2012-05-11 2015-04-29 艾伯维公司 作为nampt抑制剂的哒嗪和吡啶衍生物

Patent Citations (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995007271A1 (fr) 1993-09-09 1995-03-16 The Upjohn Company Agents antimicrobiens oxazolidinone a substitution oxazine et thiazine
WO1997010223A1 (fr) 1995-09-15 1997-03-20 Pharmacia & Upjohn Company Aminoryle oxazolidinone n-oxydes
US7521421B2 (en) 1997-10-08 2009-04-21 Isotechnika Inc. Deuterated cyclosporine analogs and methods of making the same
US7538189B2 (en) 1997-10-08 2009-05-26 Isotechnika Inc. Methods of making deuterated cyclosporin analogs
US7534814B2 (en) 1999-07-30 2009-05-19 Nabriva Therapeutics Ag Mutilin derivatives and their use as antibacterials
WO2003074500A2 (fr) * 2002-03-06 2003-09-12 Sanofi-Aventis Nouveaux composes
WO2005016915A1 (fr) * 2003-08-14 2005-02-24 Glaxo Group Limited Derives carboxamides de piperidine/cyclohexane destines a etre utilises comme modulateurs du recepteur vanilloide
EP1700856A1 (fr) * 2003-12-26 2006-09-13 Kyowa Hakko Kogyo Co., Ltd. Derive de thiazole
WO2005099353A2 (fr) 2004-04-19 2005-10-27 Symed Labs Limited Nouveau procede pour preparer du linezolide et des composes associes
WO2006008754A1 (fr) 2004-07-20 2006-01-26 Symed Labs Limited Nouveaux intermediaires pour linezolide et composes correspondants
US7511013B2 (en) 2004-09-29 2009-03-31 Amr Technology, Inc. Cyclosporin analogues and their pharmaceutical uses
US20090111840A1 (en) 2005-05-31 2009-04-30 Peter Herold Heterocyclic spiro-compounds as aldosterone synthase inhibitors
US7514068B2 (en) 2005-09-14 2009-04-07 Concert Pharmaceuticals Inc. Biphenyl-pyrazolecarboxamide compounds
US20090093422A1 (en) 2006-10-23 2009-04-09 Roger Tung Oxazolidinone derivatives and methods of use
US20090105307A1 (en) 2007-02-15 2009-04-23 Guido Galley 2-aminooxazolines as taar1 ligands
US7528131B2 (en) 2007-04-19 2009-05-05 Concert Pharmaceuticals Inc. Substituted morpholinyl compounds
US7531685B2 (en) 2007-06-01 2009-05-12 Protia, Llc Deuterium-enriched oxybutynin
US20090131485A1 (en) 2007-09-10 2009-05-21 Concert Pharmaceuticals, Inc. Deuterated pirfenidone
US20090118238A1 (en) 2007-09-17 2009-05-07 Protia, Llc Deuterium-enriched alendronate
US20090082471A1 (en) 2007-09-26 2009-03-26 Protia, Llc Deuterium-enriched fingolimod
US20090088416A1 (en) 2007-09-26 2009-04-02 Protia, Llc Deuterium-enriched lapaquistat
US20090137457A1 (en) 2007-10-02 2009-05-28 Concert Pharmaceuticals, Inc. Pyrimidinedione derivatives
US20090105147A1 (en) 2007-10-18 2009-04-23 Concert Pharmaceuticals Inc. Deuterated etravirine
US20090105338A1 (en) 2007-10-18 2009-04-23 Protia, Llc Deuterium-enriched gabexate mesylate
US20090131363A1 (en) 2007-10-26 2009-05-21 Harbeson Scott L Deuterated darunavir
WO2011025799A1 (fr) * 2009-08-26 2011-03-03 Glaxo Group Limited Inhibiteurs de cathepsine c
WO2012031199A1 (fr) * 2010-09-03 2012-03-08 Forma Therapeutics, Inc. Composés et compositions de guanidine pour l'inhibition de nampt

Non-Patent Citations (22)

* Cited by examiner, † Cited by third party
Title
ADYA, R., DIABETES CARE, vol. 31, 2008, pages 758 - 760
BLAGOJEVIC N ET AL.: "Dosimetry & Treatment Planning for Neutron Capture Therapy", 1994, ADVANCED MEDICAL PUBLISHING, pages: 125 - 134
BLAKE ET AL., J. PHARM. SCI., vol. 64, no. 3, 1975, pages 367 - 391
BRICKNER, S J ET AL., J MED CHEM, vol. 39, no. 3, 1996, pages 673
BRUZZONE, S ET AL., PLOS ONE, vol. 4, 2009, pages E7897
CZAJKA D M; FINKEL A J, ANN. N.Y. ACAD. SCI., vol. 84, 1960, pages 770
CZAKJA D M ET AL., AM. J. PHYSIOL., vol. 201, 1961, pages 357
DIABETES METAB., vol. 23, 1997, pages 251
FOSTER ET AL.: "Advances in Drug Research", vol. 14, 1985, ACADEMIC PRESS, pages: 2 - 36
GALLI, M. ET AL., CANCER RES., vol. 70, 2010, pages 8 - 11
GARTEN, A. ET AL., TRENDS IN ENDOCRINOLOGY AND METABOLISM, vol. 20, 2008, pages 130 - 138
HANSEN, CM ET AL., ANTICANCER RES., vol. 20, 2000, pages 42111 - 4220
KATO ET AL., J. LABELLED COMP. RADIOPHARMACEUT., vol. 36, no. 10, 1995, pages 927 - 932
KIM, S.R. ET AL., BIOCHEM. BIOPHYS. RES. C'OMMUN., vol. 357, 2007, pages 150 - 156
KUSHNER ET AL., CAN. J. PHYSIOL. PHARMACOL., vol. 77, 1999, pages 79 - 88
LIZONDO, J ET AL., DRUGS FUT, vol. 21, no. 11, 1996, pages 1116
MALLCSHAM, B, ORG LETT, vol. 5, no. 7, 2003, pages 963
OLESE, U.H. ET AL., MOL CANCER THER., vol. 9, 2010, pages 1609 - 1617
See also references of EP2847181A1 *
THOMSON J F, ANN. NEW YORK ACAD. SCI, vol. 84, 1960, pages 736
VAN BEIJNUM, J.R. ET AL., INT. J. CANCER, vol. 101, 2002, pages 118 - 127
ZIEGKEL, M., EUR. I BIOCHEM., vol. 267, 2000, pages 1550 - 1564

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10144742B2 (en) 2014-04-18 2018-12-04 Millennium Pharmaceuticals, Inc. Quinoxaline compounds and uses thereof
US11958850B2 (en) 2014-06-19 2024-04-16 Takeda Pharmaceutical Company Limited Heteroaryl compounds for kinase inhibition
US9796712B2 (en) 2014-06-19 2017-10-24 Ariad Pharmaceuticals, Inc. Heteroaryl compounds for kinase inhibition
US10227342B2 (en) 2014-06-19 2019-03-12 Ariad Pharmaceuticals, Inc. Heteroaryl compounds for kinase inhibition
US10323018B2 (en) 2015-01-20 2019-06-18 Millennium Pharmaceuticals, Inc. Quinazoline and quinoline compounds and uses thereof
US11021514B2 (en) 2016-06-01 2021-06-01 Athira Pharma, Inc. Compounds
US11638762B2 (en) 2016-10-18 2023-05-02 Seagen Inc. Targeted delivery of nicotinamide adenine dinucleotide salvage pathway inhibitors
WO2018124001A1 (fr) 2016-12-27 2018-07-05 国立研究開発法人理化学研究所 Composé inhibiteur de signal bmp
WO2018177993A1 (fr) 2017-03-31 2018-10-04 Bayer Cropscience Aktiengesellschaft Pyrazoles pour lutter contre les arthropodes
US11931414B2 (en) 2017-04-27 2024-03-19 Seagen Inc. Quaternized nicotinamide adenine dinucleotide salvage pathway inhibitor conjugates
US11555029B2 (en) 2018-02-13 2023-01-17 Gilead Sciences, Inc. PD-1/PD-L1 inhibitors
US10710986B2 (en) 2018-02-13 2020-07-14 Gilead Sciences, Inc. PD-1/PD-L1 inhibitors
US10899735B2 (en) 2018-04-19 2021-01-26 Gilead Sciences, Inc. PD-1/PD-L1 inhibitors
US12084431B2 (en) 2018-05-14 2024-09-10 Takeda Pharmaceutical Company Limited Pharmaceutical salts of pyrimidine derivatives and method of treating disorders
US10774071B2 (en) 2018-07-13 2020-09-15 Gilead Sciences, Inc. PD-1/PD-L1 inhibitors
US12269812B2 (en) 2018-07-13 2025-04-08 Gilead Sciences, Inc. PD-1/PD-L1 inhibitors
US11236085B2 (en) 2018-10-24 2022-02-01 Gilead Sciences, Inc. PD-1/PD-L1 inhibitors
WO2020179859A1 (fr) 2019-03-06 2020-09-10 第一三共株式会社 Dérivé de pyrrolopyrazole
US11807626B2 (en) 2020-04-23 2023-11-07 Opna Bio SA Compounds and methods for CD73 modulation and indications therefor
US12202818B2 (en) 2020-04-23 2025-01-21 Opna Bio SA Compounds and methods for CD73 modulation and indications therefor
US11345681B1 (en) 2020-06-05 2022-05-31 Kinnate Biopharma Inc. Inhibitors of fibroblast growth factor receptor kinases

Also Published As

Publication number Publication date
MX2014013751A (es) 2015-08-07
US20150141398A1 (en) 2015-05-21
CN104583194A (zh) 2015-04-29
EP2847181A1 (fr) 2015-03-18
HK1209739A1 (en) 2016-04-08
US8975398B2 (en) 2015-03-10
TW201350478A (zh) 2013-12-16
JP2015520752A (ja) 2015-07-23
US20130303509A1 (en) 2013-11-14
AR091023A1 (es) 2014-12-30
US20130303510A1 (en) 2013-11-14
US20170065575A1 (en) 2017-03-09
CA2873097A1 (fr) 2013-11-14
UY34804A (es) 2013-12-31

Similar Documents

Publication Publication Date Title
US8975398B2 (en) NAMPT inhibitors
US10093624B2 (en) NAMPT and ROCK inhibitors
US9193723B2 (en) NAMPT inhibitors
WO2013170113A1 (fr) Inhibiteurs de nampt
US9796708B2 (en) Pyrrolo [2,3-B] pyridine CDK9 kinase inhibitors
WO2014139328A1 (fr) Inhibiteurs de pyrrolo[2,3-b]pyridine cdk9 kinase
US20160193209A1 (en) Nampt inhibitors
US9758511B2 (en) NAMPT inhibitors

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 13726339

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2873097

Country of ref document: CA

ENP Entry into the national phase

Ref document number: 2015511730

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: MX/A/2014/013751

Country of ref document: MX

WWE Wipo information: entry into national phase

Ref document number: 2013726339

Country of ref document: EP

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载